ApoA-IV has many structural and functional properties in common with apoA- I, is found primarily in HDL, and has been proposed to be important in both triglyceride metabolism and reverse cholesterol transport. ApoA-IV is a polymorphic apolipoprotein and the molecular basis of several isoforms has been determined. The apoA-IV-2 isoprotein has been associated with lower triglyceride and higher HDL levels than the most common apoA-IV-1 isoprotein. We have established that both forms of apoA- IV are catabolized extremely rapidly in normal subjects, with a mean fractional catabolic rate of greater than 2 pools/day, making apoa-IV the most rapidly catabolized apolipoprotein analyzed to date. The apoA-IV-2 isoprotein has a slower catabolic rate than apoA-IV-1, consistent with its different in vitro properties. ApoA-IV plasma levels are positively associated with plasma triglyceride levels. We determined using both exogenously-labeled radiotracers and endogenous labeling with stable isotopes that the catabolic rate of apoA-IV was markedly delayed compared with normal. Hence, the higher apoA-IV levels seen with higher levels of triglycerides are due to a delay in the rate of apoA-IV catabolism, rather than an increased synthetic rate of this apolipoprotein. Ongoing studies are directed toward establishing the importance of apoB-containing lipoproteins in apoA-IV metabolism and investigating the metabolism of apoA-IV in HDL deficiency states. These studies included subjects of age 18 to 42 years. 30% of the study subjects were women, and one was African-American.